Cardiovascular disease is the leading cause of death in the United States and many other countries. Nutritional factors are widely recognized as playing a role in preventing, delaying the onset of and/or slowing the progression of arteriosclerosis and coronary heart disease.
Most risk markers for cardiovascular disease have a pro-inflammatory component, which stimulates the release of a number of active molecules such as inflammatory mediators, reactive oxygen species, nitric oxide, and peroxynitrite from endothelial, vascular smooth muscle, and immune cells in response to injury (reviewed by Osiecki, Altern Med Rev. 2004 March; 9(1):32–53). Nutrients such as arginine, antioxidants (vitamins C and E, lipoic acid, glutathione), and enzyme cofactors (vitamins B2 and B3, folate, and tetrahydrobiopterin) help to elevate nitric oxide levels and may play an important role in the management of cardiovascular disease. Other dietary components such as DHA/EPA from fish oil, tocotrienols, vitamins B6 and B12, and quercetin contribute further to mitigating the inflammatory process.
Aspirin has a role in the prevention of cardiovascular and cerebrovascular disease, Alzheimer's dementia and several cancers. Encouraging all 50 year olds to take low-dose aspirin doubles their chances of living a healthy life into their nineties. The widespread use of aspirin, however, is limited as many older subjects are currently unable to take aspirin because of gastrointestinal side-effects. A review by Newton et al. (Aliment Pharmacol Ther. 2004 Jan. 1; 19(1):39–45) explores why gastrointestinal events occur with aspirin use and how a net benefit from prophylactic aspirin might be achieved in older subjects. It is suggested that, by understanding the age-related changes in upper gastrointestinal physiology and the mechanisms by which aspirin leads to the risk reductions associated with its use, it may be possible to direct interventions to improve tolerability in older subjects.
Aspirin (acetylsalicylic acid), the most widely used antiplatelet drug, is clinically effective for the prevention of vascular ischaemic events (reviewed by Mahe et al. Drugs Aging, 2003; 20(13):999–1010). Very few primary or secondary prevention trials address the benefit-risk ratio of aspirin in the elderly. In secondary prevention, it is generally accepted that the beneficial effect of aspirin in the general patient population, demonstrated by randomised controlled trials, can be extrapolated to the elderly. Elderly patients are at relatively high risk for the development of vascular disease and might also be expected to derive substantial benefit from regular aspirin administration. Retrospective studies in the elderly found that the benefit provided by aspirin in older patients was similar or increased compared with younger individuals. In primary prevention, the potential benefit of antiplatelet agents must be balanced against the risk of bleeding, which is higher in older patients.
The gastro-intestinal (GI) toxicity associated with high dose aspirin has been fully demonstrated, but remains poorly elucidated at low doses i.e., less than 500 mg/day (reviewed by Sibilia et al., Presse Med. 2003 Nov. 22; 32(37 Pt 2):S17–28). Such toxicity is relatively difficult to study because lesional and/or bleeding GI complications are not always well described in studies. The GI risk exists, starting with the lowest doses and appears to be dose-dependent. The lesional complications consist mainly of erosive lesions, most often gastric, and rarely true ulcers. Cases of bleeding appear more frequent, but generally are minor.
Low-dose aspirin is an important therapeutic option in the prevention of cardiovascular disease, including myocardial infarction and ischemic stroke, especially in light of its unique cost-effectiveness and widespread availability (reviewed by Gorelick & Weisman, Stroke. 2005 August; 36(8):1801–7. Epub 2005 Jul. 14). In the secondary prevention of cardiovascular, cerebrovascular, and ischemic events, the evidence supports that the benefits of aspirin treatment significantly outweigh the risk of a major hemorrhage.
Attempts have been made to design multivitamin supplements specifically for heart health. Examples include U.S. Pat. No. 5,770,215, which relates to a multivitamin composition containing various vitamins, minerals, and acetylsalicylic acid, U.S. Pat. No. 5,948,443, which pertains to an acetylsalicylic acid and micronutrient supplement, U.S. Pat. No. 6,914,073 which relates to a composition containing a high level of Vitamin B in encapsulated form, U.S. Pat. No. 6,953,593, which pertains to a microencapsulation process or a sustained release formulation for oral delivery with a microencapsulated core material, International Patent Publication WO 98/41195, which encompasses a nutritional supplement containing at least one flavonoid and folic acid or folate, International Patent Publication WO 03/030818 and related U.S. patent application Ser. Nos. 10/264,205 and 10/864,149, which pertain to active agent compositions using liposome beads and International Patent Publication No. WO 03/020260 and related U.S. patent application Ser. Nos. 11/141,085 and 10/234,002, which pertain to compositions comprising at least one arginine compound or conjugate thereof and at least one member selected from the group consisting of high molecular weight aliphatic alcohol and methyl donor cofactor and conjugates thereof and methods of using the same.
There is a need for formulations with a low dose of aspirin with supplements to limit gastrointestinal toxicity to prevent cardiovascular disease.
Citation or identification of any document in this application is not an admission that such document is available as prior art to the present invention.